The pharmaceutical compositions which have been used as gastric antisecretory and spasmolytic agents have been such as atropine, homatropine, propantheline bromide, dicyclomine hydrochloride and other compounds which are structurally dissimilar to the biguanides of this invention. Due to the anticholinergic properties of these compounds they are known to produce undesirable side effects such as mydriasis, xerostomia, cyclopegia and other unwanted effects.
There have been a number of 1-aryl biguanides described in the literature. They have been proposed for use as antidiabetics, anorexigenic or antimalarial agents. J. H. Burn and J. R. Vane, however, in the Brit. J. Pharmacol. (1948), 3:346-9 tested 1-(p-chlorophenyl)biguanide for its ability to reduce gastric secretion. Their findings determined that little or no reduction of gastric secretion was associated with this compound. Contrary to this belief:
We have unexpectedly found that when an alkyl group is present in a halophenyl biguanide compound valuable pharmacologic properties exist and these compounds then unexpectedly possess useful gastric antisecretory and spasmolytic properties.
We have also found that the compounds of this invention are substantially free of the anticholinergic side-effects which accompany gastric antisecretory and spasmolytic agents.
We have further found that the compounds of this invention have a low order of toxicity.
We have still further found a simple and effective method for treating gastrointenstinal disorders and diseases, such as duodenal and peptic ulcers.
We have found that the 1-substituted phenyl biguanides of this invention also have an effective degree of antihypertensive and CNS depressant activity.